This project is central to the Conte center. All other projects are linked to this project in a conceptual[unreadable] and a practical sense. This project follows up on our findings that lesions disrupt the functioning of[unreadable] the mood circuit in elderly patients with depression. The project utilizes multimodal imaging Diffusion[unreadable] tensor imaging (DTI), magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS)[unreadable] along with cognitive testing and genetics to study the connectivity and dysregulation of the mood[unreadable] circuit. Based on findings from our earlier work we evaluate the nature of the changes in the fiber[unreadable] tracts connecting amygdala, Orbital prefrontal cortex, dorsolateral prefrontal cortex, striatum and its[unreadable] relationship to neurocognitive changes. We evaluate whether glutamate is[unreadable] reduced in the anterior cingulate and orbital prefrontal cortex in patients with depression using MRS.[unreadable] In addition we evaluate changes in brain structure and function as it relates to serotonin transporter[unreadable] promoter region allelic variants. This project uses state of the art image processing and will lead to a[unreadable] greater understanding of the neuroanatomical substrates of depression.